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(1)

THE INFLUENCE OF INTRACARDIAC

BARORECEPTORS ON VENOUS RETURN,

SYSTEMIC VASCULAR VOLUME AND

PERIPHERAL RESISTANCE

John Ross Jr., … , Charles J. Frahm, Eugene Braunwald

J Clin Invest. 1961;40(3):563-572. https://doi.org/10.1172/JCI104284.

Research Article

Find the latest version:

http://jci.me/104284/pdf

(2)

THE INFLUENCE OF INTRACARDIAC BARORECEPTORS ON VENOUS RETURN, SYSTEMIC VASCULAR VOLUME

AND PERIPHERAL RESISTANCE

By JOHN ROSS, JR., CHARLES J. FRAHM AND EUGENE BRAUNWALD

(Fromn the Section of Cardiology, Clinic of Surgery, National Heart Institute, Bethesda, Md.)

(Submitted for publication August 10, 1960; accepted November 3, 1960)

The presence of baroreceptors in the walls of the cardiac chambers and the pulmonary vascular

bed is now well established, and their function in the reflex control of the circulation has been the

subject of a number of investigations (1-11).

Action potentials have been recorded from af-ferent fibers originating in the heart and lungs

(1, 2), and elevation of pressures within the ven-tricular chambers (3-9) and pulmonary

vascu-lar bed (4, 10, 11) has resulted in bradycardia (3-10), a decline in systemic arterial pressure (4-9, 11), and either apnea (5, 10) or hyperpnea (4, 11). In a previous report from this labora-tory, evidence was presented that the carotid baroreceptors reflexly influence total venous

re-turn and systemic vascular volume (12). The present investigations were undertaken to deter-mine whether or not these hemodynamic param-etersarealso modified by activation of intracardiac baroreceptors. Studies to localize these receptors within the heart were also carried out.

METHODS

Seventeen dogs weighingfrom 15.1 to23.0 kg,average,

17.2, were anesthetized with morphine (2 mg per kg),

chloralose (48 mg per kg), and urethan (480 mg per

kg). Following tracheal intubation, a bilateral thoraco-tomywas performed through the fourth intercostal space and the sternum was transected. Heparin (2 mg per kg) was then administered intravenously. The femoral artery was cannulated, large cannulae were inserted into each vena cava through the right atrium, and total body perfusion was carried out with a pump-oxygenator

sys-tem as described elsewhere (13). Briefly, blood was

drained by gravity from the venae cavae into a rotating

disc oxygenator and was returned to the femoral artery bymeansof aroller pump througha recording rotameter

(14) whichcontinuouslymetered theperfusion rate.

Sys-temicperfusionrates rangedfrom 73to 109 andaveraged

96 ml per kg. Blood temperature was maintained

be-tween 340 and 37° C bymeans of a heating coil around the oxygenator. In 10 dogs, measurements of altera-tions in the volume of blood in the extracorporeal cir-cuit were carried out. Changes in the level of blood in

the oxygenator were detected by means of sensing elec-trodes (15), and blood was added to or removed from

a calibrated reservoir so that the volume of blood in the oxygenator remained constant. Alterations in

extra-corporeal blood volume, which reflected reciprocal changes in the intravascular blood volume, were meas-ured by recording the level in the calibrated reservoir at 1 minute intervals. In 3 animals, intravascular blood was maintained at a constant volume by increasing or decreasing the arterial pump output; with this maneuver the effect of any intervention on venous return could be determined (16). For example, when venous return to the oxygenator diminished, the pump output was de-creased manually at a rate sufficient to maintain the vol-ume of the extracorporeal circuit constant.

Pressures were measured in the aorta and the inferior vena cava through catheters inserted into small branches of the femoral artery and vein; pressures in the right and left ventricles were obtained by means of catheters inserted directly through the ventricular walls, and in the left atrium by means of a catheter introduced through a pulmonary vein. All pressures were measured with Statham pressure transducers and were recorded

con-tinuously, together with the systemic perfusion rate, on a multichannel oscillograph. Since the systemic per-fusion rate was held constant throughout each experi-ment, any change in arterial pressure reflected an iden-tical change in peripheral resistance.

In order to study the reflex effects of changes in in-tracardiac pressure, two types of preparations were em-ployed. In the first preparation, utilized in Dogs 14, 15

and 16 (TableI),the aorta wasoccluded above the

coro-naryarteries, andbloodwas suppliedtothe heartthrough

a line which originated between the pump and the flow-meter. Total systemic perfusion rate was held constant.

In these experiments, blood entered the left ventricle through a cannula which had been inserted through the apex. The rate of blood flow into the heart, which de-termined the pressure in the left side of the heart, was

regulated by means of a screw clamp on the inflow line. This bloodwas pumped by the left ventricle into the

aor-tic segment proximal to the occlusive clamp, thence

through the coronary circulation, and was returned to

the pump oxygenator by means of a large drainage tube placed in theright ventricle via the azygos veina-nd right atrium. Although this preparation was satisfactory for

studying the effects of changes in intracardiac- pressures

on peripheral resistance, it was unsuitable for the meas-urement of alterations of intravascular blood:volume and

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JOHN ROSS, JR., CHARLES J. FRAHM AND EUGENE BRAUNWALD

venous return; when the blood flow to the heart was

in-creased, a significant volume was necessarily diverted

from the extracorporeal circuit into the cardiac cham-bers and pulmonary circulation.

Accordingly, in the second preparation, blood was

cir-culated through the heart by utilizing a separate circuit, entirely isolated from the pump-oxygenator system

(Fig-ure 1). Oxygenated blood drained from a reservoir

through a cannulated pulmonary vein and into the left

side of the heart. In addition to the drainage cannula placed in the right ventricle, a tube was inserted into a

segmental pulmonary artery to assure complete

empty-ing of the right heart and pulmonary artery; the blood from these two drainage tubes was collected in an acces-sory reservoir. Circulation through the lungs was

pre-vented by mass ligation of each hilum. Alterations in pressure inthe left side of the heart could be induced by

varying the inflow fromthe reservoir while the ascending

aorta was kept clamped. When the inflow of blood to

the pulmonary vein was increased, left heart pressures rose, since the only egress of blood was through the

coronary bed. Pressure in the right side of the heart

could be modified by varying the resistance in the right ventricular and pulmonary arterial drainage lines, since clamping of the lines resulted in a "damming up" of

blood in the right side of the heart. When left ventricu-lar systolic pressure was maintained at a level exceeding

approximately 70 mm Hg, the heart continued to beat satisfactorily for several hours. During each

experi-ment, control pressures, extracorporeal blood volume

and heart rate were determined for at least 4 minutes,

and following each intervention, measurements were

re-corded continuously for another 4 to 8 minutes. This preparation was employed in 14 dogs, two of which (7

and 8, Table I) had been subjected to splenectomy

sev-eral weeks prior to study.

In an effort to define the activity of the intracardiac

receptors more precisely, bilateral mass ligation of the

carotid bulb was performed in the 3 dogs in which the

first preparation was employed and in 10 of the 14

ex-periments utilizing the second preparation. In 9 of the

10 dogs in the lattergroup, the aortic baroreceptors were

TABLE I

Hemodynamic effects of changes inintracardiacpressures

LV press. LApress. RV press. Ao press. HR

Dog __

Intervention no. Wt A B A B A B A B AB.V. AS.F. A B

kg mmHg cmH20 mmHg mmHg ml mi/min

i+ 19.0 70/6 200/17 8 23 25/3 60/20 66 40 +160 126 120

75/0 210/10 10 22 25/2 75/15 75 50 -220 210/10 65/0 22 10 75/15 20/5 50 69 + 70

2+ 16.6 75/1 220/15 6 14 12/9 85/25 120 90 96 102

3+ 19.0 68/3 190/5 6 20 2/0 60/5 84 60 -540

Left andright 190/5 75/5 20 6 60/5 2/0 60 74 +260

heart pressures 4+ 23.0 77/5 235/22 6 25 1/0 60/10 67 50 -590 120 120

altered 235/30 60/5 25 5 60/10 1/0 58 68 +195 120 132

100/8 225/40 8 40 1/0 60/10 63 52 +110 114 114

5 18.3 73/7 225/20 7 30 1/0 70/18 63 50 +170

6 17.6 70/6 180/20 10 30 3/0 75/17 74 63 +135 126 114

7 16.5 95/5 230/30 5 35 5/0 80/13 67 50 + 90 120 114

8 15.1 92/8 230/35 9 40 1/0 65/15 78 66 +110 102 102

9+ 20.5 75/10 115/30 8 40 1/0 5/0 68 45 118 108

10+ 16.7 80/6 200/30 7 40 2/0 2/0 84 65 + 90

11+ 15.3 110/5 225/30 5 47 5/0 10/0 102 70 + 40 108 108

12+ 15.5 85/3 225/12 3 16 5/0 5/0 110 66 84 78

Leftheart 200/22 80/2 33 5 5/0 7/0 90 115 111 111

pressureonly 13+ 19.5 80/5 240/35 5 35 10/0 10/0 112 90 +120

altered 240/35 55/5 35 3 10/0 10/0 90 97 105 120

14=F 12.2 57/3 175/2 5 7- 135 105

15F 16.2 65/0 177/4 0 4 89 75

16=F 15.6 75/0 170/3 0 0 93 78

17F 15.4 80/0 175/3 2 6 20/3 22/3 113 75 +170 120 120

5 85/11 95/13 9 11 1/0 60/11 67 63 132 120

Rightheart 6 105/6 110/0 8 8 1/0 73/14 65 62 132 144

pressure only 11 137/12 137/10 12 11 1/0 55/8 88 88 120 116

altered 12 80/2 75/5 5 5 7/0 85/15 112 107 99 111

13 100/9 100/8 9 9 10/5 65/11 102 99 132 126

*LV =left ventricular pressure; LA =mean left atrial pressure; RV = right ventricular pressure; Ao = mean

aortic pressure; HR = Heart rate inbeats per minute. Columns A represent observations during the control period;

Brepresent the observations madefollowingalteration ofintracardiac pressure. A B.V. = thechange in systemic vascu-larvolume;AS.F. =thechangeinsystemic flow; + = carotid and aortic receptors denervated; F =carotid receptors only denervated.

(4)

HEMODYNAMIC INFLUENCES OF INTRACARDIAC BARORECEPTORS

:I

Se.i, Rot.

FIG. 1. SCHEMATIC REPRESENTATION OF THE

EXTRA-CORPOREAL CIRCUIT EMPLOYED. Blood drains by gravity

from the superior vena cava (SVC) and the inferior vena cava (IVC) into the oxygenator. The aorta (Ao.)

is cross-clamped above the coronary arteries. The level

of blood in the oxygenator is sensed by the detecting

electrodes (Det.) and blood is added to or withdrawn

from the calibrated reservoir (Res.) at the lower right-hand corner. Oxygenated blood is pumped through a

rotameter (Rot.) into the femoral artery (FA). Inter-mittently,aclamp onthe fillingline (Fill. line) isopened to permit replenishmentof the top reservoir (Res.) with

oxygenated blood.

also removed by stripping the adventitia from the

an-terior surface of the aorta between the brachiocephalic

and subclavian arteries (Table I).

At the conclusion of 6 experiments, the line through

which blood entered the left atrium from the reservoir

was occluded, resulting in anoxic cardiac arrest or

ven-tricular fibrillation. Alterations in arterial pressure were

recorded continuously for several minutes thereafter,

while systemic perfusion rate was maintained constant.

RESULTS

I. Alterations in systemic blood volume. In

all ten of the dogs in which blood volume altera-tions were measured (Table I), elevation of

in-tracardiac pressures resulted in a decline in the

extracorporeal volume and, therefore, an

augmen-tation of intravascular blood volume,whichranged from 40 to 170 ml and averaged 120 ml. A trac-ing from an experiment ofthis type is reproduced in Figure 2. In six of these animals (Dogs 1, 4-8), the pressures in the right side of the heart, the leftatrium and the left ventriclewereelevated,

and in four (Dogs 10, 11, 13, 17), the pressure

elevationwas confined to the left sideof the heart,

while right heart pressures were not altered.

The increments of intravascular volume observed in these two groups of experiments were similar.

The changes in blood volume persisted for the

en-tireperiod that the intracardiac pressureremained elevated, which in some experiments was up to

15 minutes.

II. Alterations in venous return. In Dogs 1, 3 and 4 the pressures inboth the right and left sides

of the heart were elevated. In order to maintain the extracorporeal, and therefore the intravascu-lar, blood volume constant. it was necessary to

diminish the output of thepump by 590, 540, and

220 ml per minute; this represented an average

decrease of 25.3 per cent from the control

sys-temic perfusion rates. When intracardiac pres-sures were lowered to their previous levels, ve-nous return increased but did not return to the

control levels (Figure3, Table I).

III. Alterations in systemic vascular resistance.

In Dogs

1-8,

left ventricular pressure was

ele-vated from average values of 78/5 to 216/21 mm

Hg; mean left atrial pressure rose from an aver-age of 7 to an average of 25 cm H2O, and right ventricular pressure rose from average values of 6/1 to69/15 mm Hg. These pressure alterations resultedin adeclineinsystemic vascular resistance whichwas maximal approximately 1 minute later.

These maximal changes in systemic vascular

re-sistance ranged from 10 to 39 per cent and

aver-aged 24 per cent of the control resistance levels. Subsequently, the arterial pressure returned

par-tially toward control levels (Figures 2 and 4). This return was less prominent in those dogs which had undergone sinoaortic denervation.

In five experiments (Dogs 9-13) right

ven-tricular pressure was maintained constant at a low level (Table I), while left ventricular pres-sure was elevated from average values of 86/6 to

203/26 mm Hg, and mean left atrial pressure rose from an average of6 to an average of 36 cm

HO. This again resulted in a declineinsystemic vascular resistance which ranged from 20 to 40

per cent and averaged 30 per cent of the control resistance levels.

In four experiments (Dogs 14-17) left ven-tricular systolic pressure alone was elevated.

Pressure in this chamber rose from average val-ues of 69/1 to 175/3 mm Hg, while left atrial

(5)

JOHN ROSS, JR., CHARLES J. FRAHM AND EUGENE BRAUNWALD

A.

ml.

150-

100-50

-0

B.

A BLOOD VOLUME

4

; .

wl~

I

Control 0 5 10

Minutes

FIG. 2. DOG 6. A. RECORDINGS, FROM ABOVE DOWNWARD, OF PRESSURE IN THE AORTA (Ao.),

SYSTEMIC FLOW (S.F.), PRESSURES IN THE LEFT VENTRICLE (LV) AND RIGHT VENTRICLE (RV). Inthe panelon the left,left ventricular pressure was elevated. Six minutes later, in the center

panel, rightventricular pressure was alsoelevated. In the panelon theright, ventricular pres-sures were lowered.

B. THE ALTERATIONS IN SYSTEMIC VASCULAR VOLUME WHICH OCCURRED SIMULTANEOUSLY ARE

DEPICTED. The vertical arrows indicate the points in time at which left and then right ventric-ular pressures were elevated.

pressure remained low and changed little or not at all. In all of these dogs the right ventricle was decompressed with a large drainage cannula, and

intheone dog in which right ventricular pressure was measured, it did not rise. These elevations

in left ventricular systolic pressure alone resulted

in a decline in systemic vascular resistance which

ranged from 16 to 38 per cent (average, 23) of

the control resistance levels (Figure 4). In two

other experiments when left ventricular systolic

pressure was elevated from levels below 70 mm

Hg to systolic pressures of 131 and 150mm Hg, systemic vascular resistance declined 9.6 and 11.8per cent.

-LO--I -9 0. W

(6)

HENMODYNAMIC INFLUENCES OF INTRACARDIAC BARORECEPTORS

In the entire series of experiments it was ob-served that the occurrence of ventricular

extra-systoles

wNas accompanied by a brief but striking

decline in systemic vascular resistance (Figures

3 and 5A).

I'. Alterations in heiart rate. The effects of the elevations in intracardiac pressures on heart rate were variable and slight (Table I). In

seven

experiments

the rate declined by more than 5 beats per minute; in five experiments it rose by

L.A. cm.H20

10-

O-Ao.

mm.Hg.

Mrw'0.

50

0

mm.Hg

200-FIG. 3. DOG 1. THE EFFECTS OF ELEVATIONS OF PRES-SURES IN THE RIGHT VENTRICLE (RV), LEFT ATRIUM

(LA) AND LEFT VENTRICLE (LV), ACCOMPANIED BY EX-TRASYSTOLES, ON TOTAL VENOUS RETURN, AS MEASURED BY ALTERING SYSTEMIC PERFUSION RATE (S.F.). The latter

declined after intracardiac pressures were elevated and returned toward the control levels following the

reduc-tion of these pressures.

In five experiments (Dogs 5, 6, 11-13) right ventricular pressure was elevated from average

values of 4/1 to 68/12 mm Hg, while left atrial

and left ventricular pressures were maintained at

relatively constant levels. Peripheral resistance declined by only 0 to 5 per cent, with an average

fall of 3 per cent from control levels (Figure 5).

S.F ml./min.

1000

500-.

LV

mm.

H,9.

150-

-100-

_

50!

0

1

1

FIG. 4. DOG 17. ALTERATIONS IN AORTIC PRESSURE

(Ao.) AT A CONSTANT SYSTEMIC FLOW (S.F.) FOLLOWING

ELEVATION OF LEFT VENTRICULAR (LV) SYSTOLIC

PRES-SURE, ACCOMIPANIED BY A MINIMIAL ELEVATION OF LEFT

VENTRICULAR DIASTOLIC AND NIEAN LEFT ATRIAL (LA)

PRESSURE.

R.V mm.Hg.

75

-

50-

25-0

L.A.

cm.H20[

20-o-,

Ao. mm.Hg.1

50

-0

S. F

ml./min.

2000-I

(7)

JOHN ROSS, JR., CHARLES J. FRAHM AND EUGENE BRAUNWALD

i.H9.~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

...

DO-Wi

....,-50 i

FIG. 5. DOG 6. A. MINIMAL ALERATIONS IN AORTIC PRESSURE ACCOMPANYING ELEVATION OF RIGHT VENTRICULAR

PRESSURES. A more marked decline occurs near the end of thetracing following a series of extrasystoles.

B. THE EFFECT OF ALTERNATELY ELEVATING RIGHT VENTRICULAR (RV) AND LEFT VENTRICULAR (LV) PRESSURES ON

AORTIC PRESSURE (Ao.) ARE CONTRASTED. Little change results fromgradually elevating RV pressure, but a striking fall occurs when LV pressure is increased.

more than 5 beats per minute; in six it changed less than 5 beats per minute; and in two the

changes were inconsistent. The specific

cham-bers in which pressures were elevated did not ap-pear to influence these results.

V.

Effects

of cessation

of flow

to the heart. In six experiments, when the inflow of blood to the

heart was suddenly

terminated,

left ventricular

TABLE II

Hemodynamic effects ofcessationofflow

tothe heart*

LV press. LA press. Aopress.

Dog Increase

no. A B A B A B Ao press.

mmHg cmH20 mmHg %

1 85/6 6/0 8 6 65 98 51

5 75/9 1/0 8.5 0 70 82 17

6 83/7 1/0 10 6.5 64 73 14

8 87/6 8/5 10 7 88 113 28

11 83/7 1/0 10 6.5 94 105 12

13 75/7 0/0 7.5 3.5 90 115 29

*ColumnsA representobservations madejustpriortocessationof

flowtothe heart. ColumnsB representobservations made following stabilization ofall pressures several minutesfollowingcessationof flow.

pressure declined abruptly from an average value of 81/7 mm Hg, and reached levels of less than 8/5 mm Hg within several minutes after cessa-tion of the heart beat. Right ventricular systolic pressure was less than 9 mm Hg prior to the ces-sation of perfusion and showed no significant change (Table II). In each dog systemic vas-cular resistance increased immediately, continued

torise for approximately 5 minutes and stabilized thereafter (Figure 6). These increases in sys-temic vascular resistance ranged from 14 to 51 per

centand averaged 25 per centofthe control values.

DISCUSSION

(8)

HEMODYNAMIC INFLUENCES OF INTRACARDIAC BARORECEPTORS

L.A.

cm.H20

20-

1

0-Ao.

50

50

100

Ln___..V

CESSATIONHOF9CARDIAC

:L 4-

=-FI._-_-DO 8_.EFET ON AORTI PRESSUR (Ao....

_-l-DECLINE IN INTRACARDIAC PRESSURE. Cardiac perfusion.

was stopped at the instant that the left ventricular and

left atrial pressures began to fall. An immediate

ele-vation of aortic pressure is evident.

the preparation, these interventions were found necessary to investigate the nature of the

periph-eral circulatory changes following alteration of intracardiac pressures.

.It was observed that a substantial decline in

venous returnresulted when pressures in the right

and left ventricles were elevated. The significance

of these changes in venous return is indicated by

the large changes in the output of the

extracor-poreal pump which were necessary to obviate any

alterations in intravascular blood volume. These

changes in pump output provide a measurement

of the decrease in cardiac output that would have occurred had the heart responded passively to the reflex changeinvenous return. Inaddition, when

systemic perfusion was maintained constant,

ele-vation of left heart pressures alone, or of both

left and right heart pressures, resulted in an

ex-pansion of the intravascular blood volume.

In-creases in blood volume have also been recently reported by Salisbury, Cross, and Rieben

follow-ing distention of the left ventricle with a balloon (8). Klussman, Van Citters and Rushmer, on

the other hand, did not demonstrate any changes in limb circumference or liver diameter when suction devices were applied to portions of the cardiac walls (17).

The changes in venous return and systemic blood volume following elevations of intracardiac pressures reported herein resemble those thatwere

observed when pressure withinthe isolated carotid

sinuses were elevated or when the vasodilating drug, Arfonad, was administered (12). It was previously suggested that these alterations in ve-nous return and systemic blood volume are most

likely due to dilatation of the systemic venous bed (12), because of 1) the large magnitude of the alterations in systemic vascular volume which oc-curred, and2) the fact that only 15 ml per kg of blood is estimated to be contained in the arterial and arteriolar vascular beds of the dog (18). Furthermore, arterial pressure varied inversely with total systemic blood volume, and it is there-fore possible that thechanges in the volume of the prearteriolar bed were actually opposite in direc-tion to the alteradirec-tions in total systemic blood volume. From the data presented above, it also

appears likely that an inhibition of venous tone

resulted from stimulation of the intracardiac

baroreceptors. Since splenic volume is known to

vary with alterations in sympathetic tone (19), it is of interest that the changes in blood volume resulting from elevating intracardiac pressures

were also observed in the dogs that had been

splenectomizedpreviously.

Reflexes originating from the left side of the

heart were first clearly demonstrated by Aviado and Schmidt (5). In the present experiments, when left ventricular systolic pressure was ele-vated but only minimal change in left ventricular

diastolic and left atrial mean pressures occurred, systemic vascular resistance declined. These ob-servations suggest the presence of left ventricu-lar baroreceptors sensitive to changes in systolic pressure. Indeed, bursts ofimpulses during early systole have been recorded from cardiac afferent nerve fibers by several investigators (1, 2). However, since some enlargement of the left

(9)

JOHN ROSS, JR., CHARLES J. FRAHM AND EUGENE BRAUNWALD

of left atrial pressure, the stimulation of left atrial receptors responsive to volume changes (20) can-not be completely excluded except in that ex-periment (Dog 16) in which isolated left ven-tricular perfusion resulted in absolutely no change in left atrial pressure. More striking alterations in vascular resistance were induced when left ventricular diastolic and left atrial pressures were

elevated above 10mm Hg (Figure 7). Since the hilaof the lungs were ligated in all of the experi-ments carried out on Dog 2, the large pulmonary veinsweredistended together with the left atrium. Previous studies have suggested that the pulmo-nary veins (4, 10, 11, 21 ), as well as the left atrium (7, 20) contain baroreceptor endings, and it is likely that receptors in both of these areas

participated in the observed reflexes.

Contrary to the observations of others (4, 11), only minimal declines in vascular resistance

oc-curredwhen,in the absence ofextrasystoles

(Fig-ure 5), pressures in the right side of the heart

alone were elevated. However, in the present

ex-periments, ligation of the hila prevented pressure elevation in the smaller pulmonary vessels, which perhaps contain receptors responsible for the de-cline in peripheral resistance observed by others when right heart pressures were elevated (11). In addition, in the present studies, right ventricu-lar diastolic and atrial pressures were only moder-ately elevated and provided a less extreme stimu-lus than that utilized in previous investigations (4). Accordingly, it is suggested from the pres-ent experiments that the intracardiac receptors of greatest importance in the control of systemic vascular resistance are those sensitive to elevation of left ventricular diastolic pressure and/or left atrial pressure. It is possible that the ultimate stimulus for these receptors is the stretch that occurs when the volume of the cardiac chambers is increased. However, the possibility that baro-receptors in the coronary vessels are also of

im-portance has not been excluded, since elevation

* I I. * *-- E ,1-...' 1,, a__ 1.__ n__L.vL_I... ... :

FIG. 7. DOG 2. TRACING SHOWING THE EFFECTS ON AORTIC PRESSURE OF STEP-WISE ELEVATION OF INTRACARDIAC

PRESSURES. The most profounddecline of aortic pressure occurred following elevation of mean left atrial (LA)

(10)

HEMODYNAMIC INFLUENCES OF INTRACARDIAC BARORECEPTORS

of left ventricular systolic pressure simultaneously raised the pressure in the coronary system.

It was observed that systemic vascular resist-ance fell when left ventricular systolic pressure was elevated in the range below the normal systolic blood pressure for the dog. This suggests that the left-sided intracardiac baroreceptors possess a low pressure threshold and, therefore, that these re-ceptors may be continuously activated at normal intracardiac pressures. This possibility receives support from experiments in which rhythmic im-pulses, synchronous with both ventricular and atrial contractions, were recorded from cardiac af-ferent fibers (1, 2, 9). Furthermore, the initial rapid rise in arterial pressure (Figure 6) which occurred following cessation of cardiac perfusion suggests that a continuous inhibitory influence on vascular resistance originating from the heart had beenremoved; this observation provides additional evidence for tonic activity of the intracardiac

re-ceptors. The continued and progressive elevation in arterial pressure, following cessation of cardiac perfusion, however, may have resulted from

stimulation by anoxia of receptors in the myo-cardium or coronary arteries.

In interpreting the action of reflexes originating from intracardiac receptors, the important effects of extrasystoles must be emphasized. It was ob-served in the course of these experiments that whenever extrasystoles occurred, whether during right- or left-sided pressure elevation, a striking decline in vascular resistance took place. This finding suggests that the intracardiac receptors, like those in the carotid sinus (22), are activated by rapid fluctuations in stimulation, regardless of the mean level of the stimulus applied. The oc-currence of extrasystoles during elevations in right heart pressure thus make interpretation of subsequent reflex changes difficult, and may help

to explain the results obtained by some previous investigators (4, 11).

The reflex effects of the intracardiac

barorecep-tors may be of importance in a variety of

physio-logic andpathologiccircumstances. It wouldseem

likely that they operate in conjunction with the sinoaortic mechanism in theregulation ofboth

ar-teriolar and venous tone and therefore of arterial pressure and cardiac output. In addition, when intracardiac pressures aloneare elevated, as in the presence of congestive heart failure or valvular

stenosis, the resulting arteriolar and venous dilata-tion could serve to decrease the hemodynamic burden imposed on the heart both by diminishing systemic pressure and by decreasing venous return.

SUM MARY

The effects of alterations of intracardiac pres-sures on total venous return, system vascular vol-ume and peripheral vascular resistance were stud-ied in an experimental canine preparation. The systemic vascular bed was perfused, using an ex-tracorporeal circulation, while pressures were in-dependently varied in the innervated, but hemo-dynamically isolated heart.

Elevation of intracardiac pressure (either in all four chambers or only in the left side of the heart) in ten dogs resulted in an augmentation of systemic vascular volume which averaged 120 ml.

Inthe three dogs in which the venous return was

measured, it declined by an average of 25 per

cent fromthe control levels. Significantdecreases in systemic vascular resistance were observed when left ventricular systolic pressures were ele-vated, when left ventricular diastolic and mean left atrial pressures were also elevated, or when extrasystoles occurred. Only minimal alterations in vascular resistance were observed to accom-pany elevation ofrightheart pressures alone.

REFERENCES

1. Whitteridge, D. Afferent nerve fibres from the heart and lungs in the cervical vagus. J. Physiol.

(Lond.) 1948, 107, 496.

2. Paintal, A. S. A study of ventricular pressure

re-ceptors and their role in the Bezold reflex. Quart. J. exp. Physiol. 1955, 40, 348.

3. Daly, I. deB., and Verney, E. B. Localisation of

re-ceptors involved in reflex regulation of heart rate.

J. Physiol. (Lond.) 1927, 62, 330.

4. Aviado, D. M., Jr., Li, T. H., Kalow, W., Schmidt, C. F., Turnbull, G. L., Peskin,G. W., Hess, M. E.,

and Weiss, A. J. Respiratory and circulatory

re-flexes from theperfused heart and pulmonary cir-culation of the dog. Amer. J. Physiol. 1951, 165,

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